1. Field of the Invention
The invention relates to a magnetic ion-exchange resin and a method for the preparation thereof, and more particularly, to a magnetic ion-exchange resin which comprises magnetic particles entrapped within the swelled ion-exchange polymer microspheres and the method for the preparation thereof.
2. The Prior Arts
The magnetic particles can control the motion of particles by external magnetic field, thereby separating and collecting biological molecules, such as cells, DNA, RNA, antibodies, antigens, proteins, and nucleic acid, which can be adsorbed onto the magnetic particles by chemical bonding or physical adsorbing and then are separating from solution. The above process can effectively separate trace amount of target material from mixture by the control of the external magnetic field, without the complicate separating processes such as filter, chromatography, centrifugation, and therefore can be widely used in the biological detection field. In addition, the magnetic particles can be used as the catalysts of biochemical reactions for capturing proteins by chemical bonding or physical adsorption and immobilizing enzyme.
Generally, the ion-exchanging resin is meant to a material with surface charge particles that can combine positive or negative ionic functional groups with resin (usually organic polymer). Ion-exchange resins have ion-exchange capabilities; it can exchange itself with the same electrical ion in the solution. According to different property of ion-exchange groups, the ion-exchange resins can be divided into cation-exchange resin and anion-exchange resin. The cation-exchange resin is known as the resin with negatively charged functional groups such as sulfonic acid on the surface thereof, and the anion-exchange resin is known as the resin with positively charged functional groups such as four amine ions. The cation-exchange resin adopts cations such as sodium ions, or hydrogen ions, and the ion-exchange principle thereof is that cations can be exchanged from the cation-exchange resin if the solution has the same cations of higher concentration or the other cations of stronger adsorption. Therefore, cations can be desorbed from the cation-exchange resin by addition of high concentration of salts (e.g. NaCl). The ion-exchange principle of anion-exchange resin is the same as that of cation-exchange resin, only with the opposite ionic charge.
The magnetic ion-exchange resin is known as combination of magnetic and ion-exchange polymer microspheres. The known manufacturing method for magnetic ion-exchange resin as disclosed in Taiwan Patent Application No. 092100312 includes the steps of: producing a dispersion having a continuous aqueous phase and a dispersed organic phase with one or more polymerizable monomers, magnetic particles and a dispersing agent, polymerizing one or more polymerizable monomers to form polymeric beads incorporating the magnetic particles. The polymeric beads include amine groups capable of complexing a transition metal cation, or the polymeric beads are reacted with one or more compounds to provide amine groups capable of complexing a transition metal cation. The polymeric beads are named as magnetic ion-exchange resin. Taiwan Patent Application No. 094108928 further discloses the separating method of transition metal ions and other ions from water solution by using this ion-exchange resin.
There are many examples that the magnetic ion-exchange resins are achieved by polymerizing magnetic particles (generally nanometer level) with a monomer and then forming polymer particles. The conventional oil in water suspension polymerization method includes the following: a monomer, magnetic nano-metal particles (iron oxide, Fe3O4, for example), an initiator, a solvent and as on fully dispersed, then are emusified to suspend in a organic phase, mixed into a water phase, finally magnetic particles are fully dispersed in an interior of magnetic polymer particles are obtained, and further the magnetic polymer particles are chemical bonded with positively charged or negatively charged ionic functional groups. Another method as disclosed in Korean patent No. KR 20040091385 comprises steps of: dispersing an organic layer consisting of magnetite, monomer and a cross-linking agent in water under nitrogen atmosphere; and after adding a polymerizable surfactant having a quaternary ammonium group and an initiating agent to the dispersion, performing a suspension polymerization to obtain a magnetic anion-exchange resin.
In addition to the conventional suspension polymerization method, the so-called spray suspension polymerization method can also be used by for example, Yang et al. This method includes the steps of applying the water solution having polyvinyl alcohol (PVA) as a water phase, and the monomer with methyl methacrylate and divinylbenzene, iron oxide (Fe3O4) coated with oleic acid, benzoyl peroxide and so on as the oil phase, under the spray of droplets in nitrogen atmosphere, forming magnetic polymer particles after polymerization, and finally obtaining a magnetic anion-exchange resin after introducing the surface amino-modification. (Yang et al., Appl. Microbiol. Biotechnol. 72 (2006) 616-622).
Heeboll-Nielsen et al. suggested a variety of production methods (Heeboll-Nielsen et al., J. Bioetchnol. 113 (2004) 247-262). One of typical methods includes providing a magnetic metal material as a core, then coating a polymer with ion-exchange function to its outer surface to form a shell. The method of China Patent No. 1680469A includes heating a thermoplastic organic polymer to molten state, mixing with magnetic particles into uniformly cross-mixing molten slurry, and then the molten slurry into the micro-droplets through pores, the micro-droplets pass through floating active elements within the ion-exchange resin, and finally collecting grains as magnetic ion-exchange resin.
Conversely, ion-exchange resin can be used as a core particle covered with a magnetic material, thereby obtaining a magnetic ion-exchange resin. For example, U.S. Pat. No. 5,595,666 A and U.S. Pat. No. 5,652,190 A disclose a weak anion exchange resin (polyamine-epichlorohydrin resin) which is covered with magnetic material (M2O2), wherein one M is iron, and the other M can be iron, barium, magnesium, calcium or similar elements. An ion-exchange resin made of cross-linking agarose also can adsorb magnetic nano-particles to form a magnetic ion-exchange resin (Nixon, et al., Chem. Mater., 4 (1992) 117-121). Zhang et al. suggests a method includes the steps of: manufacturing about 1 μm of cross-linked polymer microspheres (wherein the monomer is polyglycidyl methacrylate (PGMA) and the cross-linker is divinylbenzene), reacting with ethylenediamine to form the positively charged anion exchange resin, soaking into the solution of ferrous iron and ferric iron (FeCl3 and FeSO4), precipitating iron oxide under alkaline conditions depositing onto the anion exchange resin surface, and finally obtaining a magnetic anion exchange resin which can capture DNA (Zhang et al., J. Chromatogr. B, 877 (2009) 127-133).
In addition, U.S. Pat. No. 5,855,790 discloses a more complex method to produce magnetic particles which comprises a core of a magnetic material surrounded by a mixture of cellulous fibers and a solid binder to form a solid block of polymer. The solid block is then ground to create small particles. The iron core with its cellulose coating provides strength to the ground particles which are then functionalised. The US patent also provides an alternative method in which the polymerisation is conducted with the particles dispersed in oil, which thus creates discrete, round particles of controlled size.
Another method for manufacturing a composite magnetic ion-exchange resin includes the steps of: mixing nanosized magnetic material (such as magnetite), ion-exchange resin and polymer substrate with an appropriate solvent, spray-drying into composite particles of a magnetic ion-exchange resin, wherein the polymer substrate plays the role of bonding magnetic material and ion-exchange resin (Hickstein and Peuker, Biotechnol Prog. 24 (2008) 409-416; Kappler et al., J. Biosci. Bioeng. 105 (2008) 579-585).
U.S. Pat. No. 6,718,742 discloses a simpler method of mixing the magnetic particles (iron oxide, Fe3O4) of 5 μm or less with the granular, porous polymethacylate carboxyl ion-exchanger (negatively charged), and finally achieving a magnetic ion-exchange resin used to extract DNA. This magnetic ion-exchange resin makes the magnetic particles entrapped therein by using pore features of the polymer microspheres. Consequently, the magnetic particles easily escape from the pores of magnetic ion-exchange resin during application.
JP 2001272395 discloses a magnetic ion-exchange resin is used to separate histamine from blood, wherein histamine is quantified after desorbed from the magnetic ion-exchange resin, and then the levels of histamine in blood are learned. WO 2006/059655 provides that the mixture use of ion-exchange resin and magnetic particles can separate a microorganism or cells from samples, and extract a nucleic acid from the microorganism or the cells. Magnetic ion-exchange composites are made from the mixture of substrate, magnetic material and ion-exchange resin at a certain ratio to form amorphous particles, which were used to separate proteins (Kappler et al., J. Biosci. Bioeng. 105 (2008) 579-585).
The conventional manufacturing method of nanoscale magnetic ion-exchange resin is using nanoscale magnetic materials as a core, incorporating ion-exchange functional groups by chemical modification, and finally obtaining nano-scale magnetic ion-exchange resin. CN 1699447A discloses that iron oxide (Fe3O4) and polyacrylic acid form a covalent bond in the activation of carbonized dihydrazine, and magnetic cation-exchange resin is obtained. Negatively charged nano-magnetic ion exchange resin synthesized by binding carboxymethylated chitosan (CMCH) covalently on the surface of Fe3O4 nano-particles can be applied to separating protein (Yang et al., Ind. Eng. Chem. Res. 48 (2009) 944-950).
However, particle diameter of the above magnetic ion-exchange resins can affect the collection time, wherein the smaller particle diameter will induce the longer collection time. The conventional nanoscale ion-exchange resin has longer collection time that is impractical for biological magnetic separation. Thereby, it is necessary in the industrial development for developing a magnetic ion-exchange resin for quick separation and purification of biological molecules.